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Biomedical subjects

P Carlsson

Publications and source records attributed to P Carlsson.

At least 19 recordsLinked to original sources

Divacancy in 4H-SiC.

Electron paramagnetic resonance and ab initio supercell calculations suggest that the P6/P7 centers, which were previously assigned to the photoexcited triplet states of the carbon vacancy-antisite pairs in the double positive charge state, are related to the triplet ground states of the neutral divacancy. The spin density is found to be located mainly on three nearest C neighbors of the silicon vacancy, whereas it is negligible on the nearest Si neighbors of the carbon vacancy.

Journal Article↗

Evaluation of costs and effects of epidural analgesia and patient-controlled intravenous analgesia after major abdominal surgery.

BACKGROUND: The outcome of different treatment strategies for postoperative pain has been an issue of controversy. Apart from efficacy and effectiveness a policy decision should also consider cost-effectiveness. Since economic analyses on postoperative pain treatment are rare we developed a decision model in a pilot cost-effectiveness analysis (CEA) comparing epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) after major abdominal surgery in routine care. METHODS: Using a decision-tree model, treatment with EDA (ropivacaine and morphine) was compared with PCIA (morphine). Effects and costs of treatment were established. The number of pain-free days at rest (pain intensity <30 using visual analogue scale 1-100 mm) was the primary measure of effect. An incremental cost-effectiveness ratio (ICER) was calculated as the difference in direct costs divided by the difference in effect. A database on 644 patients collected for the purpose of quality control during the period of 1997 to 1999 was the main data source. Sensitivity analysis was used to test uncertain data. RESULTS: EDA was more effective in terms of pain-free days but more expensive. The additional cost for each pain-free day was 5652 Euros. CONCLUSION: It is a judgement of value if the additional cost is reasonable. When the cost of around 55,000 Euros per gained life-year with full health for other interventions is debated, our result indicates poor cost-effectiveness for EDA. Before any conclusion can be drawn concerning policy recommendations the difference in costs has to be related to other outcome measures as length of hospital stay, morbidity and mortality are required.

Abdomen↗

Food habits and appetite of elderly women at the time of a femoral neck fracture and after nutritional and anabolic support.

OBJECTIVE: To study appetite and food choices in lean elderly women at the time of a femoral neck fracture and after 6 months of nutritional and anabolic intervention. SUBJECTS AND METHODS: Forty-five nondemented women >70 years of age (mean +/- SD: 83 +/- 5 years) with a recent hip fracture and body mass index <24 kg/m2 (mean: 20.5 +/- 2.3) were interviewed about their appetite and dietary habits prior to fracture. The patients were randomized to treatment with a protein-rich liquid supplement (PR; 200 kcal and 20 g protein day(-1)) alone or in combination with nandrolone decanoate injections (PR/N) 25 mg i.m. every third week or to a control group (C). A second interview was conducted 6 months later. RESULTS: Reduced appetite before the fracture was reported by 60%. Half of the patients did not have dessert with any of their daily meals, one-third used low-fat margarines and one-third drank water with their meals. The estimated mean daily energy intake was 6.4 +/- 1.2 MJ (1541 +/- 304 kcal) indicating that three of four subjects did not meet their energy needs. At 6 months, 40% reported reduced appetite. There was no difference in the change of appetite between the three randomized groups. Still, half of the subjects appeared to not meet their energy needs. Protein intake increased in the PR and PR/N groups, in contrast to the controls (P = 0.002). CONCLUSION: Reduced appetite and insufficient energy intake was recorded in lean elderly women with a femoral neck fracture. Nutritional supplementation alone or in combination with an anabolic steroid increased protein intake without adversely affecting appetite.

Aged↗

Structural investigations of polymer electrolyte poly(propylene oxide)-LiClO4 using diffraction experiments and reverse Monte Carlo simulation.

The structure of an amorphous polymer electrolyte, poly(propylene oxide) (PPO) complexed with LiClO4, has been studied using reverse Monte Carlo (RMC) simulations. The simulations require no force field but are based on experimental data only, in this case from x-ray and neutron diffraction experiments. Excellent agreement between the experimental data and the structures resulting from the RMC simulation is obtained. Samples with ether-oxygen to lithium concentrations (molar ratios) O:Li=16:1 and 5:1 were studied and compared to results of pure PPO from a previous study. We focus on the effects of the solvated salt on the structure of the polymer matrix, the spatial distribution of ions, and the correlations between the anions and the polymer chains. Analyzing the structures produced in the simulations, we find that for a concentration 16:1, the interchain distance is approximately the same as in pure PPO but more well defined. For a concentration 5:1, we find a larger and less well-defined interchain distance compared to the 16:1 concentration. This signifies that at the 16:1 salt concentration, there is enough free volume in the polymer host to accommodate the ions, and that the solvation of salt induces ordering of the polymer matrix. At the higher salt concentration 5:1, the polymer network must expand and become less ordered to host the ions. We also note, in accordance with previous studies, that the solvation of salt changes the conformation of the polymer chain towards more gauche states. The simulations furthermore reveal marked correlations between the polymer chains and the anions, which we suggest arise predominantly from an interaction mediated via cations, which can simultaneously coordinate both ether oxygens in the polymer chains and anions. Interanionic distances at 5 A, which are consistent with two or more anions being coordinated around the same cation, are also observed. On a larger scale, the RMC structure of PPO-LiClO4 16:1 clearly indicates the presence of salt-rich and salt-depleted domains having a length scale of <20 A. In view of such a heterogeneous structure of PPO-LiClO4 16:1, it is plausible that the increased ordering of the polymer matrix is due to rather well-defined structural arrangements within the salt-rich domains, and that the characteristic interchain distance in the salt-rich domains is similar to that of the pure polymer.

Journal Article↗

A population-based study of pain and quality of life during the year before death in men with prostate cancer.

In order to explore how health-related quality of life changes towards the end of life, a questionnaire including the EuroQOl form and the Brief Pain Inventory form was sent to all men with prostate cancer in the county of Ostergötland, Sweden, in September 1999. Responders who had died prior to 1 January 2001 were later identified retrospectively. Of the 1442 men who received the questionnaire, 1243 responded (86.2%). In the group of responders, 167 had died within the study period, 66 of prostate cancer. In multivariate analysis, pain as well as death within the period of study were found to predict decreased quality of life significantly. Of those who died of prostate cancer, 29.0% had rated their worst pain the previous week as severe. The same figure for those still alive was 10.5%. On a visual analogue scale (range 0-100), the mean rating of quality of life for those who subsequently died of prostate cancer was 54.0 (95% confidence interval +/-5.2) and those still alive was 70.0 (+/-1.2). In conclusion, health-related quality of life gradually declines during the last year of life in men with prostate cancer. This decline may partly be avoided by an optimised pain management.

Aged↗

Randomized clinical trial of the costs of open and laparoscopic surgery for colonic cancer.

BACKGROUND: There has been no randomized clinical trial of the costs of laparoscopic colonic resection (LCR) compared with those of open colonic resection (OCR) in the treatment of colonic cancer. METHODS: A subset of Swedish patients included in the Colon Cancer Open Or Laparoscopic Resection (COLOR) trial was included in a prospective cost analysis; costs were calculated up to 12 weeks after surgery. All relevant costs to society were included. No effects of the procedures, such as quality of life or survival, were taken into account. RESULTS: Two hundred and ten patients were included in the primary analysis, 98 of whom had LCR and 112 OCR. Total costs to society did not differ significantly between groups (difference in means for LCR versus OCR euro1846; P = 0.104). The cost of operation was significantly higher for LCR than for OCR (difference in means euro1171; P < 0.001), as was the cost of the first admission (difference in means euro1556; P = 0.015) and the total cost to the healthcare system (difference in means euro2244; P = 0.018). CONCLUSION: Within 12 weeks of surgery for colonic cancer, there was no difference in total costs to society incurred by LCR and OCR. The LCR procedure, however, was more costly to the healthcare system.

Aged↗

Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis.

Gene targeting studies indicate that sonic hedgehog (Shh) signaling plays an essential role during craniofacial development. Because numerous mandibular derivatives (e.g., teeth, tongue, Meckel's cartilage) are absent in Shh null mice and the embryonic submandibular salivary gland (SMG) develops from the mandibular arch, we postulated that Shh signaling is important for embryonic SMG development. To address this question, we first determined the spatiotemporal distribution of Shh; two transmembrane proteins, patched 1 (Ptc) and Smoothened (Smo), which act as a negative or a positive regulator of the Shh signal, respectively; and the Gli 3 transcription factor, which is downstream of the Shh signal. The epithelial localization of Shh, Ptc, Smo, and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner. The SMG phenotype in our embryonic day (E) 18.5 Shh null mice can be characterized as "paedomorphic," that is, it fails to progress to ontogenic stages beyond the Early Pseudoglandular ( approximately E14). In a complementary set of experiments, we used organ culture to evaluate the effect of enhanced or abrogated Shh signaling on embryonic SMG development in vitro. Paired E13 (Late Initial Bud stage) or E14 (Pseudoglandular stage) SMGs were cultured in the presence or absence of exogenous Shh peptide supplementation; Shh-supplemented explants exhibit a significant stage-dependent increase in branching morphogenesis compared with control explants. Furthermore, by using cyclopamine, a steroidal alkaloid that specifically disrupts the Shh pathway, to abrogate endogenous Shh signaling in vitro, we found a significant decrease in branching in cyclopamine-treated explants compared with controls, as well as a significant decrease in epithelial cell proliferation. Our results indicate that Shh signaling plays an essential role during embryonic SMG branching morphogenesis. Exogenous FGF8 peptide supplementation in vitro rescues the abnormal SMG phenotype seen in cyclopamine-treated explants, demonstrating that overexpression of a parallel, but related, downstream signaling pathway can compensate for diminished Shh signaling and restore embryonic SMG branching morphogenesis.

Animals↗

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta.

Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

Adenocarcinoma↗

Tracing genotypes of mutans streptococci on tooth sites by random amplified polymorphic DNA (RAPD) analysis.

The aim of this study was to clarify the distribution and persistence of mutans streptococci on different tooth sites in the same oral cavity. Thirteen subjects, aged 20-40 years, were examined. Salivary levels of mutans streptococci, caries prevalence, oral hygiene habits and status of tooth surfaces sampled were recorded. Plaque samples were obtained from four sites, the mesial and buccal surfaces of the first permanent molar on the right side of the lower jaw (46m and 46b), the distal surface of the first permanent premolar (24d) and the mesial surface of the second permanent premolar (25m) on the left side of the upper jaw, using sterile toothpicks on two occasions at 4-7-month intervals. The samples were cultivated on site-specific Strip mutans. Up to 10 colonies/site were isolated when present and genotyped by random amplified polymorphic DNA (RAPD) analysis, after species identification with PCR. Genotyping was also performed by restriction endonuclease analysis (REA) on 148 isolates, and results were consistent with the RAPD results. Most mutans streptococcus-positive samples were obtained from 46m. Within each individual, the same genotype occurred on at least two sites on all but one sampling occasion. A maximum of seven different genotypes were found in an individual. For a particular tooth site, four genotypes occurred simultaneously and taking both sampling occasions together the maximum was six different types. The same genotypes/types were found again after 4-7 months on 25 sites in 12 subjects. Fifteen sites were mutans streptococcus-positive on only one sampling occasion. The results indicate that several different genotypes of mutans streptococci colonize a tooth site, and that the same genotype colonizes several sites in the same oral cavity. Persistence of genotypes on a site for several months and interindividual differences in the occurrence of genotypes were also found.

Adult↗

FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance.

Obesity, hyperlipidemia, and insulin resistance are common forerunners of type 2 diabetes mellitus. We have identified the human winged helix/forkhead transcription factor gene FOXC2 as a key regulator of adipocyte metabolism. Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene expression, which leads to a lean and insulin sensitive phenotype. FOXC2 affects adipocyte metabolism by increasing the sensitivity of the beta-adrenergic-cAMP-protein kinase A (PKA) signaling pathway through alteration of adipocyte PKA holoenzyme composition. Increased FOXC2 levels, induced by high fat diet, seem to counteract most of the symptoms associated with obesity, including hypertriglyceridemia and diet-induced insulin resistance--a likely consequence hereof would be protection against type 2 diabetes.

Adipocytes↗

Pain and health-related quality of life in a geographically defined population of men with prostate cancer.

In order to provide baseline data on pain and health-related quality of life, to explore factors predicting pain and reduced quality of life, and to find potentially undertreated cases in men with prostate cancer, we undertook a population-based questionnaire study. The questionnaire, which included the EuroQo1 instrument, the Brief Pain Inventory form and 8 specially designed questions, was sent to all men with prostate cancer in the county of Ostergötland, Sweden. Of the 1442 men included in the study, 1243 responded to the questionnaire. Altogether 42% had perceived pain during the previous week and 26% stated their quality of life to be 50% or lower on a visual analogue scale. A high rating of health care availability and short time since diagnosis were found to significantly predict lower ratings of pain (P< 0.05). Pain was found to be a significant predictive factor for decreased quality of life together with high age, low rating of health care availability and palliative treatment (P< 0.05). In conclusion, assessment and treatment of pain is essential for a good quality of life in men with prostate cancer. The monitoring of prostate cancer patients should be individualized to fit the demands of the groups with the greatest need for support.

Aged↗

Different methods for toxin analysis in the cyanobacterium Nodularia spumigena (Cyanophyceae).

The brackish water cyanobacterium Nodularia spumigena produce the hepatotoxic cyclic pentapeptide nodularin. Intoxications for both human as well as animal may arise when water reservoirs are contaminated with potentially toxic Nodularia species. Here, results of three independent methods for the determination of nodularin in different strains of N. spumigena are presented. The results obtained with a protein phosphatase assay and a HPLC/UV/MS method are compared with the results obtained with a bioluminescence assay, which is successfully introduced here for nodularin determination. Statistical evaluation of the three applied methods revealed a good comparability towards the detected toxin content. The methods were evaluated taking into consideration the parameters: handling, efficiency, sensitivity and selectivity. The detection limit in the protein phosphatase assay is highest (0.05ng nodularin) and lowest (250ng nodularin) in the bioluminescence assay- it was determined with 5ng (MS) and 25ng (UV) for the HPLC/UV/MS methods. The different selectivities and sensitivities are critically discussed and an analytical pathway for the determination of the biotoxin nodularin from Nodularia samples is proposed.

Chromatography, High Pressure Liquid↗

Quality indicators for health promotion programmes.

Methods for systematically following up and auditing health promotion have been in demand for a considerable period of time. Quality assurance as an auditing method has opened up new opportunities in this area. On the basis of Donabedian's 'triad' of structure, process and outcome, the theoretical preconditions for and implementation of a number of successful health promotion programmes/ projects have been analysed with regard to their common characteristics. These characteristics have been generalized and then transformed into indicators of a successful health promotion programme/project. To ensure the practical applicability of the quality indicators, they were operationalized in what we call a 'question pro-forma'. Any negative response to a question on the pro-forma indicates quality defects in a programme, and any positive response the opposite. The 'template' can be employed for both the planning and auditing for quality assurance on health promotion programmes and projects. The question pro-forma has been tested successfully on a number of programmes and projects. The results from one study are shown in the article.

Health Promotion↗

Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations.

The murine Foxf1 gene, encoding a forkhead - or winged helix - transcription factor, is expressed in splanchnic mesenchyme during organogenesis. The concentration of expression to subepithelial mesenchyme suggested that Foxf1 is activated by paracrine signals from endodermal epithelia. Homozygous Foxf1-null mice die before embryonic day 10, owing to defects in extra-embryonic mesoderm, and do not provide any information about the role of Foxf1 in morphogenesis of endodermally derived organs. We show that, on CD1 genetic background, Foxf1 heterozygote perinatal mortality is around 90%. The haploinsufficiency causes a variable phenotype that includes lung immaturity and hypoplasia, fusion of right lung lobes, narrowing of esophagus and trachea, esophageal atresia and tracheo-esophageal fistula. Similar malformations are observed in mutants that are defective in the sonic hedgehog (Shh) signaling pathway, and we show that exogenous Shh activates transcription of Foxf1 in developing lung. Foxf1 mRNA is absent in the lungs, foregut and sclerotomes of Shh(-/-) embryos, but persists in tissues where indian hedgehog (Ihh) is expressed. In lung organ cultures, activation of Foxf1 by Shh is counteracted by bone morphogenetic protein 4 (BMP4). Fibroblast growth factor (FGF) 10 and FGF7 both decrease Foxf1 expression and we speculate that this is mediated by transcriptional activation of epithelial Bmp4 (in the case of FGF10) and by inhibition of Shh expression for FGF7.

Animals↗

The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm.

The murine Foxf1 gene encodes a forkhead transcription factor expressed in extra-embryonic and lateral plate mesoderm and later in splanchnic mesenchyme surrounding the gut and its derivatives. We have disrupted Foxf1 and show that mutant embryos die at midgestation due to defects in mesodermal differentiation and cell adhesion. The embryos do not turn and become deformed by the constraints of a small, inflexible amnion. Extra-embryonic structures exhibit a number of differentiation defects: no vasculogenesis occurs in yolk sac or allantois; chorioallantoic fusion fails; the amnion does not expand with the growth of the embryo, but misexpresses vascular and hematopoietic markers. Separation of the bulk of yolk sac mesoderm from the endodermal layer and adherence between mesoderm of yolk sac and amnion, indicate altered cell adhesion properties and enhanced intramesodermal cohesion. A possible cause of this is misexpression of the cell-adhesion protein VCAM1 in Foxf1-deficient extra-embryonic mesoderm, which leads to co-expression of VCAM with its receptor, alpha(4)-integrin. The expression level of Bmp4 is decreased in the posterior part of the embryo proper. Consistent with this, mesodermal proliferation in the primitive streak is reduced and somite formation is retarded. Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively. In Foxf1-deficient embryos incomplete separation of splanchnic and somatic mesoderm is accompanied by misexpression of Irx3 in the splanchnopleure, which implicates Foxf1 as a repressor of Irx3 and as a factor involved in coelom formation.

Allantois↗